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Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications.
J Intern Med. 2013 Oct; 274(4):331-41.JI

Abstract

OBJECTIVE

The long-term effects of enzyme-replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease affects progression towards 'hard' clinical end-points in comparison with the natural course of the disease.

METHODS

A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end-stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain.

RESULTS

During a median follow-up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end-diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow-up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min(-1) per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry.

CONCLUSION

Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease.

Authors+Show Affiliations

Department of Medicine, Divisions of Cardiology and Nephrology, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23586858

Citation

Weidemann, F, et al. "Long-term Outcome of Enzyme-replacement Therapy in Advanced Fabry Disease: Evidence for Disease Progression Towards Serious Complications." Journal of Internal Medicine, vol. 274, no. 4, 2013, pp. 331-41.
Weidemann F, Niemann M, Störk S, et al. Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications. J Intern Med. 2013;274(4):331-41.
Weidemann, F., Niemann, M., Störk, S., Breunig, F., Beer, M., Sommer, C., Herrmann, S., Ertl, G., & Wanner, C. (2013). Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications. Journal of Internal Medicine, 274(4), 331-41. https://doi.org/10.1111/joim.12077
Weidemann F, et al. Long-term Outcome of Enzyme-replacement Therapy in Advanced Fabry Disease: Evidence for Disease Progression Towards Serious Complications. J Intern Med. 2013;274(4):331-41. PubMed PMID: 23586858.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications. AU - Weidemann,F, AU - Niemann,M, AU - Störk,S, AU - Breunig,F, AU - Beer,M, AU - Sommer,C, AU - Herrmann,S, AU - Ertl,G, AU - Wanner,C, Y1 - 2013/05/06/ PY - 2013/4/17/entrez PY - 2013/4/17/pubmed PY - 2013/10/30/medline KW - Fabry disease KW - dialysis KW - prognosis KW - stroke KW - sudden cardiac death KW - α-galactosidase A SP - 331 EP - 41 JF - Journal of internal medicine JO - J. Intern. Med. VL - 274 IS - 4 N2 - OBJECTIVE: The long-term effects of enzyme-replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease affects progression towards 'hard' clinical end-points in comparison with the natural course of the disease. METHODS: A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end-stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain. RESULTS: During a median follow-up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end-diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow-up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min(-1) per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry. CONCLUSION: Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease. SN - 1365-2796 UR - https://www.unboundmedicine.com/medline/citation/23586858/Long_term_outcome_of_enzyme_replacement_therapy_in_advanced_Fabry_disease:_evidence_for_disease_progression_towards_serious_complications_ L2 - https://doi.org/10.1111/joim.12077 DB - PRIME DP - Unbound Medicine ER -